CANNABINOID MODULATION OF HYPERALGESIA

描述：(改编自《调查者摘要》) 持续性疼痛和皮肤痛觉过敏与许多疼痛有关 综合症。传统的疼痛管理方法，如使用麻醉剂， 由于它们的不良副作用，如耐受性和附加性，存在问题。 大麻类药物的止痛特性已被公认多年。 但直到最近，潜在的神经机制才开始 已澄清。尽管传统上认为大麻类物质会产生 它们通过中枢神经系统的作用而具有抗伤害性， 最近的证据表明，大麻类物质可能产生抗伤害作用。 在外围。此外，低剂量的大麻素可能对 缓解痛觉过敏。 拟议的研究将调查周围神经机制， 有助于大麻素介导的抗伤害作用。我们的初步数据 提示：1)大麻样受体位于背根神经节。 含有降钙素基因相关肽(CGRP)的神经元；2)足底 鞘内注射大麻素可防止 辣椒素引起的痛敏反应；3)大麻素减少诱发的释放 从培养的背根神经节神经元中提取GCRP。为进一步研究心力衰竭的外周机制 大麻素的抗伤害作用，我们建议：确定抗痛觉过敏 使用辣椒素和辣椒素的足底和鞘内大麻的性质 角叉菜胶炎症模型(目标1)；确定大麻素是否 减少辣椒素和辣椒素对皮肤伤害性感受器的致敏作用 卡拉胶(目标2)；以及确定大麻类物质是否会减少递质 从初级传入纤维的体外和体内释放，并研究 潜在的机制。 这些研究将提供有关以下机制的新信息 大麻素能产生抗伤害作用。此外，结果将直接 大麻素通过外周减轻痛觉过敏的临床意义 机械装置。外周大麻素可能非常有效地管理 慢性疼痛，无不良副作用，与传统 治疗。

DESCRIPTION: (Adapted from the Investigator's Abstract) Persistent pain and cutaneous hyperalgesia are associated with many painful syndromes. Traditional pain management approaches, such as with narcotics, are problematic due to their adverse side effects such as tolerance and addition. Analgesic properties of cannabinoid drugs have been acknowledged for many years but it is only recently that the underlying neural mechanisms are being elucidated. Although cannabinoids have been traditionally believed to produce their antinociceptive properties through actions in the central nervous system, recent evidence suggests that cannabinoids may produce antinociception peripherally. Moreover, low doses of cannabinoids may be very effective in relieving hyperalgesia. The proposed studies will investigate the peripheral neural mechanisms that contribute to cannabinoid-mediated antinociception. Our preliminary data suggest that 1) cannabinoid receptors are located on dorsal root ganglion (DRG) neurons that contain calcitonin gene-related peptide (CGRP); 2) intraplantar and intrathecal injection of cannabinoids prevent the development of hyperalgesia produced by capsaicin; 3) cannabinoids decrease evoked release of GCRP from cultured DRG neurons. To further investigate peripheral mechanisms of cannabinoid antinociception, we propose: to determine antihyperalgesic properties of intarplantar and intrathecal cannabinoids using the capsaicin and carrageenan models of inflammation (Aim 1); to determine whether cannabinoids reduce sensitization of cutaneous nociceptors produced by capsaicin and carrageenan (Aim 2); and to determine whether cannabinoids decrease transmitter release from primary afferent fibers in vitro and in vivo, and investigate underlying mechanisms. These studies will provide new information on the mechanisms by which cannabinoids produce antinociception. Moreover, results will have direct clinical significance if cannabinoids attenuate hyperalgesia through peripheral mechanisms. Peripheral cannabinoids may be very effective for managing certain chronic pains without undesirable side effects associated with traditional therapies.